Analysis of a novel repulsive axon guidance protein, Draxin

在神经系统发育过程中，轴突向突触靶点的正确导航是形成精确和功能神经回路的关键步骤之一。轴突通路的选择依赖于环境分泌或膜锚定的引导线索。在这里，我们报道了一种分泌蛋白的克隆和功能鉴定，我们将其称为DRXIN(背部排斥轴突引导蛋白)。DraXIN与已知的指导信号没有序列同源性，其信使RNA在发育过程中在脊髓和脑的背侧部分瞬时表达。在鸡背侧脊髓和小鼠皮质外植体中，德拉辛诱导生长锥体塌陷并排斥轴突生长。异位表达的Draxin在体内抑制了鸡脊髓连合轴突的生长或导致了错误的路径选择。DRAXIN基因缺陷小鼠的前脑三连合体、海马连合和前连合的轴突投射均有严重缺陷。相反，缰核连合、后连合和脊髓连合似乎完好无损。因此，Draxin是一种新的化学排斥性轴突导向分子，对连合轴突起着至关重要的作用，特别是在前脑连合的发育过程中。

During nervous system development, correct navigation of axons to their synaptic targets is one of the essential steps to form precise and functional neural circuits. Axonal pathway selection depends on environmental secreted or membrane-anchored guidance cues. Here, we report the cloning and functional characterization of a secreted protein, which we call Draxin(Dorsal repulsive axon guidance protein).Draxin shares no sequence homology with known guidance cues, and its messenger RNA was expressed transiently during development in the dorsal part of the spinal cord and brain. Draxin induced growth cone collapse and repelled neurite outgrowth from explants of chick dorsal spinal cord and mouse cortex. Ectopically expressed Draxin inhibited growth or caused misrouting of chick spinal commissural axons in vivo. draxin deficient mice showed severe defects in axonal projection of all three commissures, the corpus callosum, hippocampal commissure and anterior commissure in the forebrain. In contrast, the habenular commissure, posterior commissure and spinal cord commissure seemed intact. Thus, Draxin is a novel chemorepulsive axon guidance molecule for commissural axons and play crucial roles, especially in the development of forebrain commissures.